tbuckley/cabot-search huggingface dataset:
The need to develop the career pathway in oncology as an opportunity to improve the satisfaction of young oncologists in Spain: A national survey by the Spanish Society of Medical Oncology (SEOM) + mir section.
Authors: Pablo Jiménez Labaig, Domingo Antonio Sánchez, Andrea Sesma, Alicia Quilez, Vilma Pacheco Barcia, Berta Obispo, David Paez, Maria Teresa Quintanar, Manuel Sánchez-Cánovas, Noelia Tarazona, Ana Fernandez Montes, Enriqueta Felip, Alvaro Rodriguez-Lescure, Elena Elez
Journal: Journal of Clinical Oncology (2022)

11038 Background: A long-term planning of the oncologists’ career path is essential to approach the continuous changes in the oncology field given the need of further subspecialization after the training period. Our aim is to evaluate the current professional development of young medical oncologists in Spain and seek improvement strategies to enhance their careers in order to guarantee commitment with research and improve in patient care and outcomes. Methods: The SEOM +MIR Section launched a national online survey in May 2021 aimed at young medical oncology consultants (&lt;6 years of experience) and last year medical oncology residents. Spanish professionals were invited to participate via email through the SEOM database. A descriptive analysis was performed using R software v4.1.2. Results: A total of 162 responses were eligible. 103 (64%) were women. 129 (80%) were consultants and 33 (20%) were residents. 92 (68%) performed standard clinical care and 11 (7%) research activity. 118 (73%) were subspecialized in a main area of interest and almost half of them, 70 (59%), chose it because it was the only option available after finishing residency. 87 (54%) had considered different employment opportunities other than standard clinical care and 38 (23%) showed an interest in enhancing their research activity. 141 (87%) showed relevant concern about their employment stability (table attached). 82 (51%) had considered working abroad: 33 (44%) outside European Union. The main reasons were: 132 (81%) believed the professional standing in Spain was worse than other countries, 41 (25%) thought it might increase their professional development and 33 (20%) argued for better salary conditions abroad. Among them, 21 (13%) had signed at least 4 contracts and 66 (41%) had ≥5 employment contracts in the last 5 years. 27% of respondents indicated that the figure of the boss had been the most contributing professional in their professional career. The mentor (20%) and the tutor (18%) also stand out as relevant figures in terms of professional development. Up to 27% of the sample refers not to have obtained any help from the figures mentioned. Conclusions: An absence of engagement in the long-term career paths of young medical oncologists in Spain was observed. Research is not defined in the current early professional life. Furthermore, there is a lack of contractual quality and planning for the entry into the labour market of newly trained oncologists. The lack of such a career pathway has consequences that encourage the search for employment opportunities different from clinical care and in other countries. [Table: see text]
Efficacy and safety of venetoclax in combination with azacitidine or decitabine in an outpatient setting in patients with untreated acute myeloid leukemia.
Authors: Sudhir Manda, Bertrand Marquess Anz, Christopher Benton, E. Randolph Broun, Habte Aragaw Yimer, Jason M. Melear, Jose C. Cruz, Suzanne Fanning, Jeff Porter Sharman, Kingston Kang, Anders Svensson, Madhavi Pai, George F. Geils, John Scott Renshaw, William Bruce Donnellan
Journal: Journal of Clinical Oncology (2022)

7044 Background: Venetoclax (Ven), a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine (Aza) or decitabine (Dec) is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients (pts) who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated Ven + HMA in an inpatient setting due to concerns of tumor lysis syndrome (TLS). This Phase 3b, single-arm, multicenter, open-label study (NCT03941964) evaluated the efficacy and safety of Ven + HMA in a US community-based outpatient setting. Methods: Pts with ND AML who were ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed an appropriate candidate for outpatient initiation of Ven + HMA by the investigator were eligible. Pts received Ven (400 mg) in combination with Aza (75 mg/m 2 ) or Dec (20 mg/m 2 ) for up to 6 cycles during the study period. Pts could continue receiving commercially acquired Ven after the study period. All pts received TLS prophylaxis. The primary endpoint was the composite complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) per modified International Working Group criteria. Secondary endpoints included CR or CRi rates and transfusion independence (TI). TLS was assessed per Howard criteria (Howard. N Engl J Med. 2011;364:1844). Results: At the 19 Oct 2021 cutoff date, 60 pts were enrolled and treated (Ven + Aza, n=30; Ven + Dec, n=30). Efficacy outcomes are shown in the Table. The composite CR rate was 58%. CR and CRi rates were 13% and 45%, respectively. Most pts (&gt;50%) maintained TI, and 41% and 57% of pts dependent on red blood cells or platelets, respectively, converted to TI. Bone marrow blast clearance was achieved in 42 pts (70%) at a median 26 days after treatment initiation. The most common (≥50%) AEs were anemia (75%), neutrophil count decrease (55%), white blood cell count decrease (52%), and nausea (50%). Serious AEs occurred in 67% of pts, most commonly (≥15%) febrile neutropenia (28%) and sepsis (15%). Two pts (3%) had TLS; neither event led to treatment discontinuation. Of pts who achieved blast clearance, 12/42 (29%) had a new event of myelosuppression post-blast clearance and prior to the next cycle. Conclusions: The results of this US community-based study indicate that Ven + HMA is an effective treatment option for pts with ND AML and, with appropriate TLS prophylaxis and monitoring, can safely be initiated in an outpatient setting. Clinical trial information: NCT03941964. [Table: see text]
Association of germline genetic testing results with chemotherapy regimens received by women with early-stage breast cancer.
Authors: Allison W. Kurian, Paul Abrahamse, Jennifer Lee Caswell-Jin, Ann S. Hamilton, Timothy Hofer, Kevin C Ward, Steven Katz
Journal: Journal of Clinical Oncology (2022)

10518 Background: Germline genetic testing is widespread after breast cancer diagnosis and increasingly informs treatment decisions; however, guidelines do not advise selecting chemotherapy regimens based on genetic testing results. It is unknown whether women with pathogenic variants (PVs) in BRCA1, BRCA2 ( BRCA1/2) or other cancer risk genes receive different chemotherapy regimens than women with negative genetic testing results. Methods: We linked Surveillance, Epidemiology and End Results (SEER) registry records from Georgia and California to clinical germline genetic testing results from four participating laboratories (Ambry, Bioreference/GeneDx, Invitae, and Myriad). For this analysis, we included patients who: 1) were diagnosed with stages I-III breast cancer, either hormone receptor-positive and HER2-negative (HR+HER2-) or triple-negative, in Georgia or California from 2013-2017; 2) received chemotherapy based on SEER records; and 3) linked to a genetic testing result. We further selected cases by genetic testing results: 50% PVs in BRCA1/2 or another cancer risk gene, 25% variant of uncertain significance (VUS) only and 25% negative. We extracted details of chemotherapy regimens from SEER text fields completed by registrars. We categorized regimens by drug classes reported (anthracycline, taxane, platinum, nitrogen mustard, other). We used multivariable models that controlled for age, race/ethnicity, stage, grade, surgical procedure, radiotherapy receipt and geographic site to test whether PV carriers received a more intensive chemotherapy regimen. For HR+HER2-, a more intensive regimen was defined as at least three drugs including an anthracycline and for triple-negative, as at least four drugs including an anthracycline and a platinum (versus fewer drugs). Results: 2,293 women were included, 1,451 with HR+HER2- and 842 with triple-negative disease. On multivariable analysis, receipt of a more intensive chemotherapy regimen was associated with having a BRCA1/2 PV among women with HR+HER2- disease (odds ratio 1.22, p = 0.036), but not among women with triple-negative disease. Moreover, platinum use was elevated in BRCA1/2 PV carriers with HR+HER2- disease (from an adjusted model: BRCA1/2 PV 10.9%, other PV 3.6%, VUS 5.6%, negative 5.7%), while in BRCA1/2 PV carriers with triple-negative disease, platinum use did not vary significantly by genetic results ( BRCA1/2 27.7%, other PV 27.7%, VUS 20.9%, negative 20.7%; p = 0.025 for interaction between genetic result and subtype). Conclusions: Compared to women with negative genetic testing results, women with BRCA1/2 PVs more often received a platinum and/or an anthracycline in chemotherapy regimens for early-stage, HR+HER2- breast cancer. This suggests potential over-treatment. No differences in chemotherapy regimen by genetic testing result were observed in triple-negative disease.
Frontline treatment of follicular lymphoma with atezolizumab and obinutuzumab, with and without radiotherapy (The FLUORO study).
Authors: Eliza Anne Hawkes, Kate Manos, Richard Khor, Genevieve Douglas, Sze Ting Lee, Denise Lee, Belinda Campbell, Anneke Grobler, Michael Gilbertson, Jodie Palmer, Geoff Chong
Journal: Journal of Clinical Oncology (2022)

TPS7587 Background: Follicular lymphoma (FL) is the commonest indolent lymphoma, comprising 20% of non-Hodgkin Lymphoma, with approximately 80% of patients (pts) requiring therapy. At present, advanced stage is incurable; most pts require &gt;1 treatment. Overall response rates (ORR) to standard chemoimmunotherapy (bendamustine or CHOP with rituximab or obinutuzumab) approximate 85% with considerable toxicity (grade 3-5 in 69-75%) (Hiddemann 2018). With the FL population predominantly &gt;65 years, 10-year median survival and need for further therapy, efficacious treatments with low toxicity are desirable. PD1/PDL1 axis inhibitors are active in FL. A phase I study of obinutuzumab (O) + atezolizumab (A) induced 57% ORR in pts with rituximab-refractory FL (Palomba 2017). Our phase II ‘1 st FLOR’ study, combining nivolumab + rituximab in treatment naïve FL yielded 92% ORR, (54% Complete Response, CR). Toxicity profiles compared favourably with conventional chemotherapy: 41% grade 3-5 events (Hawkes 2021). FL is sensitive to low dose radiotherapy (RT), with abscopal effects reported, and potential to improve treatment efficacy with minimal additional toxicity when combined with PD1/PDL1 inhibitors (Sharabi 2015). This investigator initiated, multicentre single-arm phase II PET-adapted trial aims to assess the response of O + A +/- RT for treatment-naïve FL, reducing treatment-related toxicity using a chemotherapy-free, multi-modality, synergistic regimen. Methods: Eligible pts are &gt;18 years, ECOG 0-2 with untreated, biopsy proven, grade 1-3A stage II-IV FL. Exclusions are significant compressive symptoms, autoimmune disease, pneumonitis and treatment urgency. All pts receive 6 cycles (q21 days) of O 1000mg + A 1200mg (plus O given on days 8 &amp; 15 of cycle 1). Interim PET-CT is performed post cycle 2. Pts with less than CR will undergo RT (4Gy) to residual disease after cycle 3. At end of induction, responding patients will receive maintenance O (up to 12 cycles, 1000mg Q8W). Pts with significant progression will be taken off study. Total follow-up is 2 years post treatment. Primary endpoint is CR rate following 6 x O&amp;A +/- RT. Secondary endpoints include ORR, PFS, OS and adverse events. PET centres are ARTnet accredited with central analysis. An extensive exploratory biomarker substudy is planned. Sample size is 46 according to a Simon’s 2-stage design. If ≥5 positive responses (CR +/- PR) without prohibitive toxicity are seen in the first 15 pts, 31 further pts will be recruited.The trial has currently enrolled 7 pts from 4 Australian sites. Clinical trial information: NCT04962126.
Survey of biosimilar adoption across oncology pharmacy practices.
Authors: Marina Reed, Eugene Przespolewski, Mark Doughty Walsh, Michelle Amsler, Anthony George, Kristopher Attwood, Grazyna Riebandt
Journal: Journal of Clinical Oncology (2022)

e18813 Background: Use of biosimilars is an effective strategy in expanding access to care and lowering healthcare costs. Literature about the successes, challenges, and best practices of biosimilar adoption in oncology is limited. We aim to describe the current state of biosimilars in oncology practices and barriers to adoption. Methods: A 40-question survey was developed to gather information regarding biosimilar use in the following areas: formulary management, product usage, policies, technology, safety, and education. The following biosimilars were evaluated: bevacizumab (B), filgrastim (F), epoetin (E), infliximab (I), pegfilgrastim (P), rituximab (R), and trastuzumab (T). The survey was distributed to Hematology/Oncology Pharmacy Association members. Results: A total of 179 surveys were initiated, with a completion rate of 31%. Six surveys were removed due to duplication, resulting in 50 unique surveys with 21 responses (42%) from NCI-designated comprehensive cancer centers. Inpatient formulary decisions were driven by acquisition cost followed by reimbursement. In the outpatient setting, equal consideration was given to acquisition cost and reimbursement for formulary decisions. Thirty-two percent of institutions restricted biosimilars to their FDA approved indication. Sixty-six percent of institutions had a biosimilar interchangeability policy in place. For the corresponding reference products, overall average utilization of biosimilars was B 74%, F 88%, E 82%, I 57%, P 52%, R 73%, and T 71%. More than 90% of institutions had a preferred biosimilar on formulary. Based on the results, 72% stated payors specified the selection of biosimilars, and 76% stated payor reimbursement limited ability to participate in contract pricing. Insurance reimbursement was recognized as the main barrier to adoption (Table). Medication errors related to biosimilar use were reported by 26% respondents, with the most common cause listed as communication. Thirty-six percent of institutions provided education on the general use of biosimilars and 38% had biosimilar products in treatment specific education. Conclusions: Biosimilar adoption is consistent across responding institutions, with noted utilization shift towards biosimilar products compared to reference. Decisions for biosimilar adoption are made based on cost and reimbursement. Opportunities exist in the collaboration of health systems and payors to align formularies and promote safe and cost-effective care for their members.[Table: see text]
Impact of steroid use among patients with renal cell carcinoma (RCC) who develop immune-related adverse events (irAE).
Authors: Peter Zang, Karen Resnick, Travis Larsen, Shirley Ye, April Choi, Xiao Yu, Kevin Brady, Varsha Tulpule, Anishka D'souza, Gino Kim In
Journal: Journal of Clinical Oncology (2022)

4530 Background: Immune checkpoint inhibitor (ICI) therapy has become a standard therapy in the treatment of advanced renal cell carcinomas (RCC). This has led to a proportional increase in the frequency of immune related adverse events (irAE), however. While increasing evidence suggests that irAE may be correlated with benefit from ICI, the impact of steroids to mitigate irAE’s remains unclear. Methods: We analyzed records of patients with RCC treated with an ICI at the USC Norris Comprehensive Cancer Center, Keck Hospital of USC, and LAC+USC Hospital from 2015-2021. Statistical analysis was performed using R. The Kaplan-Meier model was used to calculate progression free survival (PFS) and overall survival (OS). A log-rank test was used to determine if differences in PFS/OS were statistically significant. Results: Out of a total 841 cancer patients treated with ICI, 107 RCC patients were identified. The median age was 60 (range 20-91). The two most common represented ethnicities were 48 Hispanic/Latino (44.9%) and 37 Caucasian (34.6%). The patient population include 64 male patients (59.8%) versus 43 female patients (40.2%). Most had metastatic disease (74.8%) versus local disease (25.2%), and most patients (80.4%) received ICI therapy as initial therapy. Only 6 patients (5.6%) were given combination ICI therapy. The three most common systems affected by irAE were endocrine (18.7%), dermatologic (16.8%), and renal (14.0%). Of the irAE that occurred, 21.5% were categorized as CTCAE grade III or higher. The median PFS of the irAE group was 51.8 months (95% CI 10.0 – 51.8) versus 11.2 months (95% CI 2.7 – 13.8) in the no irAE group. The median OS of the irAE group was 55.0 months (95% CI 23.9 – 55.0) versus 15.6 months (95% CI 13.5 – 23.5). The occurrence of irAE was associated with both statistically significantly increased PFS (p = 0.02) and OS (p = 0.007). The median PFS of patients receiving steroids to treat irAE was 6.5 months (95% CI 3.9 – 9.2) compared to 12.5 months (95% CI 10.4 – 12.5) in the group with irAE who did not receive steroids. The use of steroids was associated with statistically significant worse PFS (p = 0.04) and worse OS but not at statistical significance (p = 0.2). Conclusions: The occurrence of irAE was associated with improved PFS and OS in RCC patients treated with ICI. Furthermore, the use of steroids among patients with irAE was associated with worsened PFS, but not OS. Although steroids should still be used as clinically indicated for the management of irAE, clinicians should be judicious as they may blunt tumor response to ICI treatment.
Assessing the predictive value of ctDNA on relapse in patients with resected stage IB-IIIA NSCLC treated with adjuvant chemotherapy plus concomitant atezolizumab followed by atezolizumab: BTCRC LUN 19-396.
Authors: Fatemeh Ardeshir-Larijani, Nisha Anjali Mohindra, Anne M. Traynor, Jyoti Malhotra, Elaine Shum, Patrick C. Ma, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2022)

TPS8592 Background: A standard of care treatment for most patients with stage II and III non-small cell lung cancer (NSCLC) and a PD-L1 &gt; 1% is surgery followed by adjuvant (adj) histology-specific chemotherapy followed by 1 year of atezolizumab. The benefit of adding atezolizumab concomitantly to chemotherapy in the adj setting has not been reported. In addition, the optimal duration of adjuvant therapy is undefined. Emerging data have demonstrated the potential for ctDNA to predict clinical recurrence in patients with surgically resected lung, breast, and colon cancer. The current study explores the predictive value of ctDNA for early relapse in patients treated with adj chemotherapy plus atezolizumab. Methods: The LUN19-396 is a phase II biomarker study that enrolls pts with resected NSCLC stage IB (tumors ≥ 4cm), IIA, IIB, and select IIIA (T3N1-2, T4N0-2). The ctDNA will be assessed within 60 days post-surgery and then every 3 months up to 12 months. All pts will receive treatment with 4 cycles of Cisplatin 60-75mg/m2 + Docetaxel 60-75mg/m2 + Atezolizumab 1200mg IV on day 1 q 3w (for patients with squamous cell cancer) or Cisplatin 60-75mg/m2 + Pemetrexed 500mg/m2 + Atezolizumab 1200mg on day 1 IV q 3w (for patients with non-squamous cell), followed by up to 13 additional cycles of Atezolizumab 1200mg IV every 3w. This trial will enroll a total of 100 pts to achieve more than 80% power. The primary objective is to estimate the percentage of pts with detectable ctDNA after surgery who have clearance of ctDNA at designated time points during adjuvant therapy. The key secondary objective is to estimate the 1-year disease-free survival in pts with undetectable ctDNA after 4 cycles of adj chemotherapy plus atezolizumab who had detectable ctDNA after surgery. This trial has enrolled 17 pts as of February 8, 2022. Clinical trial information: NCT04367311.
A prospective exploratory clinical study of penpulimab plus anlotinib as first-line treatment for locally advanced or metastatic urothelial carcinoma.
Authors: Bo Yang, Qi Xiong, Qi Song, Yaping Long, Gang Guo, Hongzhao Li
Journal: Journal of Clinical Oncology (2022)

4567 Background: A high unmet need remains for first-line cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC).Immune checkpoint inhibitors have been implemented in the management of cisplatin-ineligible la/mUC. Penpulimab is a programmed death 1 (PD-1) inhibitor which had approved by the Chinese National Medical Products Administration (NMPA) on August 2021. Anlotinib is a novel oral multi-target tyrosine kinase inhibitor and primary targeted to VEGFR, FGFR, PDGFR and c-Kit. The current prospective single-arm phase Ⅱ clinical trial (ChiCTR1900028022) aimed to assess the efficacy and safety of penpulimab plus anlotinib as first-line therapy for la/mUC. Methods: Patients (pts) who had no prior systemic therapy and at least one measurable lesion according to RECIST v1.1 with histologically or cytologically confirmed locally advanced unresectable or metastatic urothelial carcinoma (including unresectable or metastatic urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis), 18-75 years, ECOG 0-2, were considered eligible for enrollment. Patients received 200 mg penpulimab intravenously on day 1 plus anlotinib, 8 mg oral daily for days 1-14 of a 21-day cycle until confirmed disease progression, intolerable toxicity, physician/patient decision to withdraw, or completion of 24 months of treatment. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Dec. 2021, 10 pts were enrolled, 9 pts had the best overall response assessments which inferred the ORR of 66.7%（95% CI, 29.9-92.5）and the DCR of 88.9% (PR in 6 pts and SD in 2 pts; 95% CI, 51.8-99.7). The median PFS was 8.2 months（(95% CI, 8.0-8.4). Any grades of adverse events (AEs) were observed in 90% (9/10) of pts, containing hyperthyroidism (33%), Creatinine increased (33%),haematuria (22%), anaemia (22%), hypertension (11%), fatigue (11%). High grade AEs of grade Ⅳ liver dysfunction were observed in one patient (11%). Conclusions: An effective treatment strategy for cisplatin-ineligible patients and for patients unable to receive chemotherapy is an important unmet clinical need. Penpulimab in combination with anlotinib in pts with la/mUC showed encouraging efficacy and satisfactory safety. Clinical trial information: ChiCTR1900028022.